Angle-Dependent Raman Spectra of Crystal Polymorphs of GaO: A Computational Study.

Two crystal polymorphs of GaO consisting of GaO-H and GaO-T monolayers are proposed in this study. Based on the density functional theory calculations, the phonon dispersion demonstrates that both GaO-H and GaO-T monolayers could be stable. The band gaps of GaO-H and GaO-T monolayers are 1.51 and 1.43 eV, respectively. When an external electric field is applied, the band gaps of GaO monolayers are reduced dramatically, down to 0.13 eV with the field of 0.7 V/Å. Because of the decreased symmetry of C3v under an external electric field, more peaks of Raman spectra can be obtained. The angle-dependent Raman spectra of A ' 1 1 ${{\rm{A}}{{^\prime}}_1^1 }$ and A ' 1 2 ${{\rm{A}}{{^\prime}}_1^2 }$ of GaO-H monolayer, and A 1 g 1 ${{\rm{A}}_{1{\rm{g}}}^1 }$ and A 1 g 2 ${{\rm{A}}_{1{\rm{g}}}^2 }$ of GaO-T monolayer are discussed seperately, with the incident lasers of 488 and 532 nm. Additionally, the Raman intensity distribution shows that the incident light should be parallel to the plane of the GaO monolayer to obtain more comparable Raman spectra. These investigations of the crystal polymorphs of GaO monolayers may guide the experimental investigations of GaO monolayers and potential optoelectronic applications.

Progress report on new medications for seizures and epilepsy: A summary of the 17th Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVII). I. Drugs in preclinical and early clinical development.

For >30 years, the Eilat Conference on New Antiepileptic Drugs and Devices has provided a forum for the discussion of advances in the development of new therapies for seizures and epilepsy. The EILAT XVII conference took place in Madrid, Spain, on May 5-8, 2024. Participants included basic scientists and clinical investigators from industry and academia, other health care professionals, and representatives from lay organizations. We summarize in this article information on treatments in preclinical and in early clinical development discussed at the conference. These include AMT-260, a gene therapy designed to downregulate the expression of Glu2K subunits of kainate receptors, in development for the treatment of drug-resistant seizures associated with mesial temporal sclerosis; BHV-7000, a selective activator of heteromeric Kv7.2/7.3 potassium channels, in development for the treatment of focal epilepsy; ETX101, a recombinant adeno-associated virus serotype 9 designed to increase NaV1.1 channel density in inhibitory γ-aminobutyric acidergic (GABAergic) neurons, in development for the treatment of SCN1A-positive Dravet syndrome; GAO-3-02, a compound structurally related to synaptamide, which exerts antiseizure activity at least in part through an action on cannabinoid type 2 receptors; LRP-661, a structural analogue of cannabidiol, in development for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex; OV329, a selective inactivator of GABA aminotransferase, in development for the treatment of drug-resistant seizures; PRAX-628, a functionally selective potent sodium channel modulator with preference for the hyperexcitable state of sodium channels, in development for the treatment of focal seizures; RAP-219, a selective negative allosteric modulator of transmembrane α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor regulatory protein γ-8, in development for the treatment of focal seizures; and rozanolixizumab, a humanized anti-neonatal Fc receptor monoclonal antibody, in development for the treatment of LGI1 autoimmune encephalitis. Treatments in more advanced development are summarized in Part II of this report.

Chanling Gao suppresses colorectal cancer via PI3K/Akt/mTOR pathway modulation and enhances quality of survival.

The Chinese medicine formula Chanling Gao (CLG) exhibits significant tumor inhibitory effects in colorectal cancer (CRC) nude mice. However, the detailed mechanisms remain elusive. CRC in situ nude mouse models were treated with CLG. Small animal magnetic resonance imaging (MRI) tracked tumor progression, and overall health metrics such as food and water intake, body weight, and survival were monitored. Posttreatment, tissues and blood were analyzed for indicators of tumor inhibition and systemic effects. Changes in vital organs were observed via stereoscope and hematoxylin-eosin staining. Immunohistochemistry quantified HIF-1α and P70S6K1 protein expression in xenografts. Double labeling was used to statistically analyze vascular endothelial growth factor (VEGF) and CD31 neovascularization. Enzyme-linked immunosorbent assay was used to determine the levels of VEGF, MMP-2, MMP-9, IL-6, and IL-10 in serum, tumors, and liver. Western blotting was used to assess the expression of the PI3K/Akt/mTOR signaling pathway-related factors TGF-ß1 and smad4 in liver tissues. CLG inhibited tumor growth, improved overall health metrics, and ameliorated abnormal blood cell counts in CRC nude mice. CLG significantly reduced tumor neovascularization and VEGF expression in tumors and blood. It also suppressed HIF-1α, EGFR, p-PI3K, Akt, p-Akt, and p-mTOR expression in tumors while enhancing PTEN oncogene expression. Systemic improvements were noted, with CLG limiting liver metastasis, reducing pro-inflammatory cytokines IL-6 and IL-10 in liver tissues, decreasing MMP-2 in blood and MMP-2 and MMP-9 in tumors, and inhibiting TGF-ß1 expression in liver tissues. CLG can enhance survival quality and inhibit tumor growth in CRC nude mice, likely through the regulation of the PI3K/Akt/mTOR signaling pathway.

Off-iso Winston-Lutz test on seven linear accelerators.

PURPOSE: The aim of this study is to find optimal gantry, collimator, and couch angles for performing single isocenter, multiple target stereotactic radiosurgery (SIMT-SRS). Nineteen angle sets were tested across seven linear accelerators for radiation-isocenter coincidence and off-isocenter coincidence. The off-isocenter Winston-Lutz test was performed to evaluate the accuracy of isocenter alignment for each angle set, and optimal angle sets as well as maximum off-isocenter distance to target for each angle set was determined. The influence of simulated patient weight on off-iso Winston-Lutz test accuracy was also inspected. METHOD: The SNC MultiMet-WL phantom and MultiMet-WL QA Software v2.1 were used for the direct measurement and analysis of the off-iso Winston-Lutz test (also referred to as Winston-Lutz-Gao test). A two-step method was developed to ensure precise initial placement of the target. Nineteen beams were delivered at 6X energy and 2 × 2 cm field size to each of six targets on the MultiMet Cube with couch kicks at five cardinal angles (90°, 45°, 0°, 315°, and 270°). To reduce imaging uncertainty, only EPID was used in target alignment and test image acquisition. A total of 200 Ibs (90.7 kg) of weight was also used to mimic patient weight. All tests were performed on both the free table and the weighted table. RESULTS: For two new TrueBeam machines, the maximum offset was within the 1 mm tolerance when the off-iso distance is less than 7 cm. Two older VitalBeam machines exhibited unfavorable gantry, couch, and collimator (GCC) angle sets: Linac No. 3 at (0,90,0), (0,270,0) and Linac No. 4 at (0,45,45) and (0,90,0). The C-Series Linacs failed in the majority of GCC angle sets, with Linac No. 5 exhibiting a maximum offset of 1.53 mm. Four of seven machines show a clear trend that offset increases with off-isocenter distance. Additionally, the IGRT table was less susceptible to the addition of simulated patient weight than the ExactCouch. CONCLUSION: Among the seven linear accelerators addressed, newer model machines such as the Varian TrueBeam were more precise than older models, especially in comparison to the C-Series Linacs. The newer machines are more suitable for delivering SIMT-SRS procedures in all GCC angle sets, and the results indicate that newer TrueBeams are capable of performing SIMT-SRS procedures at all angle sets for targets of off-iso distances up to 7 cm. The trend that offset between the target center and radiation field center increases with off-iso distance, however, does not always hold true across machines. This may be comprised by the EPID's severe off-axis horn effect. Lastly, the IGRT couch was less susceptible to patient weight compared to ExactCouch in the off-isocenter Winston-Lutz test.

STING-mediated inflammation contributes to Gao binge ethanol feeding model.

Alcohol metabolism causes hepatocytes to release damage-associated molecular patterns (DAMPs). This includes mitochondrial DNA (mtDNA), which is generated and released from damaged hepatocytes and contributes to liver injury by producing proinflammatory cytokines. STING is a pattern recognition receptor of DAMPs known to control the induction of innate immunity in various pathological processes. However, the expression profile and functions of STING in the Gao binge ethanol model remain poorly understood. We demonstrated that STING is upregulated in the Gao binge ethanol model. STING functions as an mtDNA sensor in the Kupffer cells of the liver and induces STING-signaling pathway-dependent inflammation and further aggravates hepatocyte apoptosis in the Gao binge ethanol model. This study provides novel insights into predicting disease progression and developing targeted therapies for alcoholic liver injury.

Restaurant-Based Measures to Control Community Transmission of COVID-19, Hong Kong.

Controlling transmission in restaurants is an important component of public health and social measures for coronavirus disease. We examined the effects of restaurant measures in Hong Kong. Our findings indicate that shortening operating hours did not have an effect on time-varying effective reproduction number when capacity was already reduced.

Progress report on new antiepileptic drugs: A summary of the Sixteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVI): I. Drugs in preclinical and early clinical development.

The Eilat Conferences have provided a forum for discussion of novel treatments of epilepsy among basic and clinical scientists, clinicians, and representatives from regulatory agencies as well as from the pharmaceutical industry for 3 decades. Initially with a focus on pharmacological treatments, the Eilat Conferences now also include sessions dedicated to devices for treatment and monitoring. The Sixteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVI) was held in Madrid, Spain, on May 22-25, 2022 and was attended by 157 delegates from 26 countries. As in previous Eilat Conferences, the core of EILAT XVI consisted of a sequence of sessions where compounds under development were presented and discussed. This progress report summarizes preclinical and, when available, phase 1 clinical data on five different investigational compounds in preclinical or early clinical development, namely GAO-3-02, GRT-X, NBI-921352 (formerly XEN901), OV329, and XEN496 (a pediatric granular formulation of retigabine/ezogabine). Overall, the data presented in this report illustrate novel strategies for developing antiseizure medications, including an interest in novel molecular targets, and a trend to pursue potential new treatments for rare and previously neglected severe epilepsy syndromes.

Association between preadmission low-density lipoprotein cholesterol concentration and risk of large intracerebral hemorrhage: Results from the Kailuan study.

BACKGROUND: To examine the association between low-density lipoprotein cholesterol (LDL-C) concentrations and the risk of a large hematoma volume after intracerebral hemorrhage (ICH). METHODS: Patients from the Kailuan study (Tangshan, China) who were hospitalized with ICH during 2006 and 2020 were included in this study. The concentration of lipid concentrations, hematoma volume and other clinical characteristics were retrospectively collected and analyzed. Hematoma volumes were measured on the first available brain scan using the ABC/2 method. LDL-C concentrations were obtained from the last physical examination before the occurrence of ICH. LDL-C concentration was categorized into four groups in accordance with the quartiles. Logistic regression was used to assess the association between LDL-C concentrations and the risk of a large hematoma volume of ≥30 ml. A generalized linear regression model was used to analyze the dose-response relationship between LDL-C concentration and hematoma volume. RESULTS: A total of 836 patients with ICH were evaluated. In the Multivariate logistic regression, compared to the second quartile of LDL_C, the first quartile of LDL_C had a significantly higher risk of a large hematoma volume (OR 2.49 [95% CI 1.54-4.01]), and the higher quartile of LDL_C is not associated with higher odds of large hematoma volume. In the generalized linear regression model, the adjusted ß for the association between LDL-C concentration and hematoma volume was 9.46 (95% confidence interval 2.87-16.04), whereas higher LDL-C concentration was not associated with a large hematoma volume. CONCLUSIONS: This study confirmed that low LDL-C concentrations prior to ICH are associated with a higher risk of a large hematoma volume.

Screening and Identification of Anti-Inflammatory Compounds from Erdong Gao via Multiple-Target-Cell Extraction Coupled with HPLC-Q-TOF-MS/MS and Their Structure-Activity Relationship.

Erdong Gao (EDG), consisting equally of roots of Asparagi Radix and Ophiopogonis Radix, is a well-known traditional Chinese formulation that has been used to treat cough and throat pain for centuries. However, the bioactive components in EDG remain to be elucidated. In this study, a rapid and effective method involving live cell bio-specific extraction and HPLC-Q-TOF-MS/MS was established to rapidly screen and identify the anti-inflammatory compounds of an EDG extract. One hundred and twenty-four components were identified in EDG extract using HPLC-Q-TOF-MS/MS analysis. After co-incubation with 16HBE, HPAEpiCs and HUVECs, which have been validated as the key target cells for pulmonary diseases, sixteen components were demonstrated to exhibit an affinity for binding to them. Furthermore, fifteen components were subsequently verified to exert anti-inflammatory effects on lipopolysaccharide (LPS)-induced 16HBE, HPAEpiCs and HUVECs via inhibiting the release of TNF-α and IL-6, indicating that nine steroidal saponins may possess potential for the treatment of lung-related diseases. Taken together, our study provides evidence that live cell biospecific extraction combined with the HPLC-Q-TOF-MS/MS technique was an efficient method for rapid screening potential bioactive components in traditional Chinese medicines and the structure activity relationship of steroidal saponins in EDG was summarized for the first time.

Ten years post-GAO assessment, FDA remains uninformed of potentially harmful GRAS substances in foods.

It has been approximately 10 years since the Government Accountability Office (GAO) published its report to Congress entitled, FDA Should Strengthen Its Oversight of Food Ingredients Determined to be Generally Recognized as Safe (GRAS), which strongly criticized FDA noting that its "oversight process does not help ensure the safety of all new GRAS determinations." Congress requested GAO to undertake this audit as a result of concerns that GRAS substances added to foods did not require FDA approval. Since 2010, FDA has addressed only a few of the criticisms regarding its process for establishing a food substance as GRAS. However, several of the most important GAO recommendations remain unaddressed, and most critically, FDA has chosen to remain uninformed about food substances self-determined as GRAS by manufacturers. In its 2016 final rule Substances Generally Recognized as Safe, FDA did not take the opportunity to include a provision for creation of a master list of all GRAS chemicals used in food, nor did the FDA request the authority to do so from Congress. FDA cannot fulfill its statutory obligation for ensuring the chemical safety of the U.S. food supply if it does not know which substances, in which quantities, have been added to foods.

Progress report on new antiepileptic drugs: A summary of the Fifteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XV). I. Drugs in preclinical and early clinical development.

Since 1992, the Eilat Conferences have provided a forum for all stakeholders in the epilepsy community to appraise the latest data on new antiepileptic drugs and emergency seizure treatments, including, in recent years, updates on progress with the development of novel monitoring and therapeutic devices. Because of the COVID-19 pandemic, the Fifteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XV) was held as a fully virtual conference on July 27-30, 2020 for the sessions on drugs and on August 3, 2020 for the sessions on devices, and was attended during the 5 days by >500 participants from 63 countries. This progress report summarizes key preclinical and initial (phase 1) clinical data on eight investigational treatments that are currently in early development, including 2-deoxy-D-glucose, GAO-3-02, JNJ-40411813, NBI-921352, NTX-001, sec-butylpropylacetamide, XEN1101, and XEN496. This report provides an overview of current scenarios in the area of treatment discovery and development. The information presented illustrates a variety of innovative strategies, including exploration of compounds with novel mechanisms of action, transplantation of interneurons into epileptogenic brain regions, and the targeting of rare, previously neglected syndromes.

Liangyi Gao extends lifespan and exerts an antiaging effect in Caenorhabditis elegans by modulating DAF-16/FOXO.

Liangyi Gao (LYG), a traditional Chinese medicine, is composed of Ginseng and Radix Rehmanniae Preparata, both of which have been shown to have antiaging properties. In Eastern countries, LYG is used to delay functional declines related to aging and has an obvious antiaging effect in clinical practice. However, little data from evidence-based medicine is available regarding whether LYG is beneficial overall, particularly with respect to lifespan, and how LYG functions. To address these issues, Caenorhabditis elegans, a useful organism for such studies, was employed to explore the antiaging effect and mechanism of LYG in this study. The results showed that LYG could obviously extend lifespan and slow aging-related declines in N2 wild-type C. elegans. To further characterize these antiaging effects and stress resistance, reproductive tests and other aging-related tests were performed. We found that LYG enhanced resistance against oxidative and thermal stress, reproduction, pharynx pumping, motility and growth in N2 wild-type C. elegans. In addition, we analyzed the mechanism for these effects by measuring the activity of superoxide dismutase (SOD) and the expression levels of aging-related genes. We found that LYG enhanced the activities of antioxidant enzymes and upregulated the genes daf-16, sod-3 and sir-2.1, which mediated stress resistance and longevity. In conclusion, LYG had robust and reproducible life-prolonging and antiaging benefits in C. elegans via DAF-16/FOXO regulation.

First-principles prediction of high oxygen-ion conductivity in trilanthanide gallates Ln3GaO6.

We systematically investigated trilanthanide gallates (Ln3GaO6) with the space group Cmc21 as oxygen-ion conductors using first-principles calculations. Six Ln3GaO6 (Ln = Nd, Gd, Tb, Ho, Dy, or Er) are both energetically and dynamically stable among 15 Ln3GaO6 compounds, which is consistent with previous experimental studies reporting successful syntheses of single phases. La3GaO6 and Lu3GaO6 may be metastable despite a slightly higher energy than those of competing reference states, as phonon calculations predict them to be dynamically stable. The formation and the migration barrier energies of an oxygen vacancy (V O) suggest that eight Ln3GaO6 (Ln = La, Nd, Gd, Tb, Ho, Dy, Er, or Lu) can act as oxygen-ion conductors based on V O. Ga plays a role of decreasing the distances between the oxygen sites of Ln3GaO6 compared with those of Ln2O3 so that a V O migrates easier with a reduced migration barrier energy. Larger oxygen-ion diffusivities and lower migration barrier energies of V O for the eight Ln3GaO6 are obtained for smaller atomic numbers of Ln having larger radii of Ln3+. Their oxygen-ion conductivities at 1000 K are predicted to have a similar order of magnitude to that of yttria-stabilized zirconia.

[Efficacy of Kangshuailing Gao on benign prostatic hyperplasia in rats].

OBJECTIVE: To investigate the effect of Kangshuailing Gao (KG) on benign prostatic hyperplasia (BPH) in rats and its action mechanisms. METHODS: Fifty BPH model rats were randomized into five groups of equal number, BPH model control, finasteride control, and high-, medium- and low-dose KG, to be treated intragastrically with distilled water, finasteride solution at 0.52 mg/kg, and KG solution at 4.16, 2.08 and 1.04 g/kg respectively once a day for 30 days consecutively. Another 10 normal healthy rats were taken as blank controls. The rats were weighed once a week during the treatment. The wet weight and index of the prostate were obtained after treatment, followed by measurement of the contents of serum estradiol (E2) and dihydrotestosterone (DHT), testosterone (T) and hypoxia-inducible factor-1α (HIF-1α) in the prostatic tissue, and observation of histomorphological changes in the prostate under the light microscope. RESULTS: Compared with the BPH model control group, high- and medium-dose KG significantly reduced the prostate wet weight (ï¼»0.84 ± 0.08ï¼½ vs ï¼»0.69 ± 0.04ï¼½ and ï¼»0.71 ± 0.07ï¼½ g, P < 0.01), the prostatic index (ï¼»0.28 ± 0.03ï¼½% vs ï¼»0.20 ± 0.02ï¼½% and ï¼»0.22 ± 0.03ï¼½%, P < 0.01), and the levels of T (ï¼»4.63 ± 1.25ï¼½ vs ï¼»2.44 ± 0.47ï¼½ and ï¼»2.91 ± 0.69ï¼½ ng/L, P < 0.01) and DHT (ï¼»154.44 ± 20.25ï¼½ vs ï¼»88.23 ± 13.63ï¼½ and ï¼»90.52 ± 16.44ï¼½ nmol/L, P < 0.01), but increased the level of E2 (ï¼»0.95 ± 0.24ï¼½ vs ï¼»1.19 ± 0.14ï¼½ and ï¼»1.20 ± 0.22ï¼½ nmol/L, P < 0.01) in the serum. High-dose KG remarkably reduced the overexpression of HIF-1α in the prostate tissue of the BPH model rats (P < 0.01) and alleviated such BPH-related symptoms as epithelium thinning, intraglandular secretion reduction, and interstitial substance decrease. CONCLUSIONS: Kangshuailing Gao acted effectively on BPH in the model rats by reducing the androgen level, balancing the estrogen/androgen ratio, and downregulating the expression of HIF-1α in the prostate tissue.

[Research of Feiliuping Gao and its combination with different types of drugs intervention on expression of PI3K/AKT/NF-κB in lung metastatic microenvironment].

The aim of this paper was to observe the effect of Feiliuping Gao and its combination with different types of drugs intervention on the expression of PI3K/AKT/NF-κB in lung metastatic microenvironment, and to reveal the advantage of Chinese medicine intervention time on the key molecule in lung metastatic microenvironment. The mouse model of Lewis lung carcinoma was established, and lung tissues were collected at 14 days, 21 days and 28 days after the intervention of Feiliuping Gao, and the expressions of PI3K, AKT and NF-κB were detected by immunohistochemistry and Western blot. At 14 days, there was no significant difference in PI3K expression between each group and the control group. The expression of AKT protein was significantly inhibited in the celecoxib (CLB) group, the Feiliuping Gao (FLP) combination with cyclophosphamide (FLP+CTX) group, and the Feiliuping Gao combination with celecoxib (FLP+CLB) group (P<0.05). The inhibition of AKT protein expression in FLP+CLB group was superior. The FLP+CLB group can inhibit the expression of NF-κB protein (P<0.05). At 21 days, compared with the control group, the expression of PI3K was inhibited in FLP group and the FLP+CTX group (P<0.05), while the expression of PI3K was best inhibited in the FLP+CLB group (P<0.001). Only the FLP+CLB group could significantly inhibit the expression of AKT protein (P<0.01). The FLP+CTX group had the best effect in inhibiting the expression of NF-κB protein (P<0.001). At 28 days, compared with the control group, the expression of PI3K and AKT was inhibited in the FLP+CLB group (P<0.001). Feiliuping ointment combination with celecoxib has an advantage in regulating the expression of PI3K/AKT/NF-κB molecules in lung metastatic microenvironment.

Modeling hydraulic transport and anaerobic uptake by PAOs and GAOs during wastewater feeding in EBPR granular sludge reactors.

New-generation bioprocesses using granular sludge aim for a high-rate removal of nutrients from wastewater with low footprint. Achieving enhanced biological phosphorus removal (EBPR) relies on the design of sludge beds and wastewater feeding conditions to optimally load the biomass and to select for polyphosphate- (PAOs) over glycogen-accumulating organisms (GAOs) and over other heterotrophs. A hydraulic-metabolic mathematical model was developed to elucidate the impact of hydraulic transport patterns and environmental conditions on the PAO/GAO competition during up-flow feeding through an EBPR granular sludge bed. Tracer experiments highlighted plug-flow regimes with dispersion under both rapid (9 m h-1 , Rebed = 1.6, Pez = 7.2, Pet = 4.6) and slow (0.9 m h-1 , Rebed = 0.2, Pez = 21.3, Pet = 3.4) feeding. Non-turbulent regimes (Rebed << 103 ) promote a safe implementation of simultaneous fill/draw. Feeding time, pH, and temperature significantly impacted bacterial competition for carbon uptake under anaerobic slow feeding. Feeding duration should be designed to avoid full depletion of intracellular storage polymers within static granules. PAOs bear twice longer feeding than GAOs by using both polyphosphate and glycogen hydrolysis to sustain anaerobic C-uptake. Alkaline conditions (pH 7.25-8.0) by, e.g., dosing lime in the feed select for PAOs independently of temperature (10-30°C). A twice higher bed is required for full anaerobic conversions at 10 rather than 20°C. Biosystem responses for anaerobic C-uptake can be anticipated using the model toward designing robust anaerobic selectors to manage the microbial resource in EBPR granular sludge. Biotechnol. Bioeng. 2017;114: 1688-1702. © 2017 Wiley Periodicals, Inc.

Enhanced biological phosphorus removal with different carbon sources.

Enhanced biological phosphorus removal (EBPR) process is one of the most economical and sustainable methods for phosphorus removal from wastewater. However, the performance of EBPR can be affected by available carbon sources types in the wastewater that may induce different functional microbial communities in the process. Glycogen accumulating organisms (GAOs) and polyphosphate accumulating organisms (PAOs) are commonly found by coexisting in the EBPR process. Predominance of GAO population may lead to EBPR failure due to the competition on carbon source with PAO without contributing phosphorus removal. Carbon sources indeed play an important role in alteration of PAOs and GAOs in EBPR processes. Various types of carbon sources have been investigated for EBPR performance. Certain carbon sources tend to enrich specific groups of GAOs and/or PAOs. This review summarizes the types of carbon sources applied in EBPR systems and highlights the roles of these carbon sources in PAO and GAO competition. Both single (e.g., acetate, propionate, glucose, ethanol, and amino acid) and complex carbon sources (e.g., yeast extract, peptone, and mixed carbon sources) are discussed in this review. Meanwhile, the environmental friendly and economical carbon sources that are derived from waste materials, such as crude glycerol and wasted sludge, are also discussed and compared.

Impact of butyrate on microbial selection in enhanced biological phosphorus removal systems.

Microbial selection in an enhanced biological phosphorus removal system was investigated in a laboratory-scale sequencing batch reactor fed exclusively with butyrate as a carbon source. As reported in the few previous studies, butyrate uptake was slow and phosphorus (P) release occurred during the entire anaerobic period. Polyphosphate-accumulating organism (PAO), i.e. Candidatus Accumulibacter phosphatis (named as Accumulibacter), glycogen-accumulating organisms (GAOs), i.e. Candidatus Competibacter phosphatis (named as Competibacter) and Defluviicoccus-related, tetrad-forming alphaproteobacteria (named as Defluviicoccus) were identified using fluorescence in situ hybridization analysis. The results show that Accumulibacter and Defluviicoccus were selected in the butyrate-fed reactor, whereas Competibacter was not selected. P removal was efficient at the beginning of the experiment with an increasing percentage relative abundance (% RA) of PAOs. The % RA of Accumulibacter and Defluviicoccus increased from 13% to 50% and 8% to 16%, respectively, and the % RA of Competibacter decreased from 8% to 2% during the experiment. After 6 weeks, P removal deteriorated with the poor correlation between the percentage of P removal and % RA of GAOs.

Ancient genomic analysis of a Chinese hereditary elite from the Northern and Southern Dynasties.

China's Northern and Southern Dynasties period (3rd-6th centuries AD) marked a significant era of ethnic integration in northern China. However, previous ancient DNA studies have primarily focused on northern ethnic groups, with limited research on the genetic formation of the hereditary elite family, especially considering their abundant archaeological record and clear material identity. In this study, we obtained the ancient genome of a hereditary elite family, Gao Bin (, 503 AD-572 AD), at 0.6473-fold coverage with 475,132 single-nucleotide polymorphisms (SNPs) on the 1240k panel. His mitochondrial haplogroup belonged to Z4 and Y-haplogroup to O1a1a2b-F2444∗. The genetic profile of Gao Bin was most similar to that of the northern Han Chinese. He could be modeled as deriving all his ancestry from Late Neolithic to Iron Age Yellow River farmers without influence from Northeast Asia, Korea, or the Mongolian Plateau. Our study sheds light on the genetic formation of hereditary elite families in the context of the Southern and Northern Dynasties ethnic integration.

Pharmacokinetics, safety, and efficacy of Fuqi Guben Gao in the treatment of kidney-yang deficiency syndrome: a randomized, double-blind phase I trial.

Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry (Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon (Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30 years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation. Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125 g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method. Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed. Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=26934, identifier ChiCTR1800015840.